We propose this exploratory project to investigate the underlying mechanism of osteoporotic vertebral fracture that is frequently observed in postmenopausal women. Osteoporosis is a metabolic bone disorder, predominantly prevalent in the elderly population. Approximately 150,000 osteoporosis-related vertebral fractures are reported annually, with expenditures for care ranging up to $14 billion per year. About 50% of the elderly female population is expected to have at least one vertebral fracture. These types of fractures will likely become more common as human life expectancy increases. Decreasing bone mass has been recognized as an indicator of bone fragility, however, loss of bone mass cannot completely account for high risk of fracture. Estrogen deficiency is most commonly observed in postmenopausal women. This female hormonal change triggers active bone turnover that inherently increases the number of trabecular packets giving rise to more variable but less degree of mineralization of bone (DMB). As the mineral in bone plays a role in maintaining mechanical strength of the bone matrix, decreases in mineral content leads to weaker bone. Increases in the number of new compartments (packets) provide more interfaces in the bone matrix. Shearing at the interfaces (cement lines) is a significant source of viscoelastic energy dissipation in bone as a composite material. Human vertebrae experience prolonged loads from upper body weight and muscle forces during daily activity. For the vertebrae that are weakened by postmenopausal active bone remodeling, these cumulative daily loads are more susceptible to vertebral fractures resulting in progressive vertebral deformation. A good example of this effect is that it is much easier to cut a rubber band when it is stretched out. Combining together the biological (active remodeling) and the mechanical (prolonged loading) aspects in postmenopausal bone, we hypothesized that active bone remodeling, which increases cement lines and variability of DMB at the bone matrix level, is responsible for residual deformation accumulation due to physiological loads at the organ level. Thus, the objective of this proposal is to investigate the mechanism of time-dependent deformation (creep) in vertebral bone at different levels of its structural hierarchy using parameters (osteocyte lacunae, cement lines and DBM) resulting from active bone remodeling. In this project, we will 1) establish the relationship of micro-CT based DMB with physiological creep, residual deformation, and fracture properties of vertebral bone at the organ level, 2) demonstrate the concentration of local creep on osteocyte lacunae and cement lines using optical analysis at the microstructural level, and 3) determine the viscoelastic properties of trabecular bone matrix at the nano-level. Identification of the macro/micro/nano-level mechanisms responsible for accumulation of creep will help accomplish our long term goal of developing a strategy to reduce fracture risk of postmenopausal bone. PUBLIC HEALTH RELEVANCE: Prolonged daily loading on a vertebral body can lead to severe vertebral deformity in osteoporotic postmenopausal women. This project is designed to investigate the role of time-dependent viscoelastic properties of bone in progressive vertebral deformation. The outcomes of this project will contribute to the development of more effective therapies for treating osteoporosis associated with estrogen deficiency in postmenopausal patients.